top 25 articles of year 2013

5/23/2018 Top 25 Articles of Year 2013

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List of Top 25 ArticlesJanuary to December 2013 Full Year


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Library Information Services, Islamabad.

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Sr. No Title

1 Users of the world, unite! The challenges and opportunities of Social Media

Abstract

The concept of Social Media is top of the agenda for many business executives today. Decision makers, as well as consultants, try to

identify ways in which firms can make profitable use of applications such as Wikipedia, YouTube, Facebook, Second Life, and Twitter. Yet

despite this interest, there seems to be very limited understanding of what the termSocial Mediaexactly means; this article intendsto provide some clarification. We begin by describing the concept of Social Media, and discuss how it differs from related concepts such as

Web 2.0 and User Generated Content. Based on this definition, we then provide a classification of Social Media which groups applications

currently subsumed under the generalized term into more specific categories by characteristic: collaborative projects, blogs, content

communities, social networking sites, virtual game worlds, and virtual social worlds. Finally, we present 10 pieces of advice for companies

which decide to utilize Social Media.

2 Potential of a Pycnoporus sanguineus laccase in bioremediation of wastewater and kinetic activation in the presence of an anthraquinonic

acid dye

Abstract

In the frame of the development of a bioprocess using the competences of White Rot Fungi to decolourise and detoxify dye contaminated

effluents, laccases were produced by the strain Pycnoporus sanguineusMUCL 41582 in a malt extract medium. Two isoenzymes were

detected among which LAC-1 was concentrated. A survey of the composition of industrial effluents showed that wastewaters from textile

industry usually contain high concentrations of Na2SO4 or NaCl. Regarding the activity profile of the biocatalyst against pH, salts,

temperature and target substrates, LAC-1 appears to be a good candidate for application in acid dye bath treatments. Studying the model

anthraquinonic dye ABu62 decolourisation, we proved that this dye was a good substrate for LAC-1. Furthermore, unusual kinetic

behaviour was observed suggesting that LAC-1 was activated in presence of ABu62. On the contrary, a classical Michaelis-Menten

behaviour was observed for the oxidation of ABTS and LAC-1 showed a high affinity for this substrate as compared to data available for

other laccases. To our knowledge, this is the first report showing this atypical behaviour of a laccase in the presence of dyes.

3 Hallmarks of Cancer: The Next Generation

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks

constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling,

evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and

metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and

inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of
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potential generality to this listreprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors

exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition

of hallmark traits by creating the tumor microenvironment.Recognition of the widespread applicability of these concepts will

increasingly affect the development of new means to treat human cancer.

4 Theoretical considerations of RES-avoiding liposomes: Molecular mechanics and chemistry of liposome interactions

Abstract

The development of long-circulating, RES-avoiding liposomes has become a remarkable milestone in the progress of contemporary

pharmacology. Drugs incorporated in such liposomes are protected from fast metabolization and c learance, and can be further targeted

to a desired tissue site. Ideally, future developments should result in drug carriers which can identify and act upon their targets with even

higher efficiency and selectivity, preferably close to or exceeding that of the natural immune cells.

Further increasing carrier `inertness' with regard to the normal biological milieu is the major requirement for future success. The ability of

natural blood components to circulate with blood for several days and weeks presents both the motivation and the challenge for further

research. Today, even the best available preparations are inferior to natural proteins and cells with regard to their ability to remain in

circulation by approximately two orders of magnitude.

In view of the above, it seems vitally important to determine the mechanisms responsible for glycolipid- or polymer-modified liposome

protection against RES, and whether any potentially useful mechanisms have been underutilized. Furthermore, identification of

quantitative dependencies between liposome structure and pharmacokinetics (and mechanisms underlying such dependencies) would

benefit future research and reduce the cost of development.

This paper discusses the relationships between liposome structure and circulation with respect to the theoretical mechanistic models of

mass transfer, liposome interactions with cells and blood proteins, and boundary effects resulting from surface modification. Special

attention is paid to the practical application and limitations of the models.

5 One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering

Summary

Mice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-

consuming intercrossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an efficient gene-targeting

technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the

simultaneous disruption of five genes (Tet1, 2 , 3, Sry, Uty - 8 alleles) in mouse embryonic stem (ES) cells with high efficiency. Coinjection

of Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2 into zygotes generated mice with biallelic mutations in both genes

with an efficiency of 80%. Finally, we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated precise point mutations

simultaneously in two target genes. Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple

genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.
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6 Social media: The new hybrid element of the promotion mix

Abstract

The emergence of Internet-based social media has made it possible for one person to communicate with hundreds or even thousands of

other people about products and the companies that provide them. Thus, the impact of consumer-to-consumer communications has been

greatly magnified in the marketplace. This article argues that social media is a hybrid element of the promotion mix because in a

traditional sense it enables companies to talk to their customers, while in a nontraditional sense it enables customers to talk directly to

one another. The content, timing, and frequency of the social media-based conversations occurring between consumers are outsidemanagersdirect control. This stands in contrast to the traditional integrated marketing communications paradigm whereby a high

degree of control is present. Therefore, managers must learn to shape consumer discussions in a manner that is consistent with the

organization's mission and performance goals. Methods by which this can be accomplished are delineated herein. They include providing

consumers with networking platforms, and using blogs, social media tools, and promotional tools to engage customers.

7 Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors

Summary

Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with

embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent

stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture

conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit themorphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice

resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to

mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by

the addition of only a few defined factors.

8 Increased intraepithelial (CD103+) CD8+ T cells in the airways of smokers with and without chronic obstructive pulmonary disease

Abstract

T cells are accumulated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Intraepithelial T cells, expressing the

integrinE (CD103)7, and regulatory T cells have been implicated in pathogenesis of the disease. We asked whether COPD patients

and smokers have altered frequencies of these T cells and if their phenotypes differ.

A total of 40 never-smokers, 40 smokers with normal lung function and 38 COPD patients (GOLD I and II), of which 11 were ex-smokers,

were included. T cells in bronchoalveolar lavage (BAL) fluid and peripheral blood were analysed for the expression of CD103, FOXP3 and

markers of activation and differentiation using multi-colour flow cytometry.

Smokers, regardless of airway obstruction, had significantly more CD8+CD103+ cells in their BAL fluid compared to never-smokers but less

of those cells were CD27+CD69. Smokers, in particular those with chronic bronchitis, had a higher percentage of CD4+FOXP3+ T-

regulatory BAL cells compared to never-smokers and COPD ex-smokers.
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Chronic cigarette smoking leads to an accumulation of CD8+ T cells with an altered phenotype in the airway epithelium. The increased

frequency of regulatory T cells may influence the ability to regulate smoke-induced inflammation which could be decisive for disease

development. Our results further indicate a reversibility of smoke-induced changes.

9 Developing a holistic strategy for integrated waste management within municipal planning: Challenges, policies, solutions and

perspectives for Hellenic municipalities in the zero-waste, low-cost direction

AbstractThe present position paper addresses contemporary waste management options, weaknesses and opportunities faced by Hellenic local

authorities. It focuses on state-of-the-art, tested as well as innovative, environmental management tools on a municipal scale and

identifies a range of different collaboration schemes between local authorities and related service providers. Currently, a policy

implementation gap is still experienced among Hellenic local authorities; it appears that administration at the local level is inadequate to

manage and implement many of the general policies proposed; identify, collect, monitor and assess relevant data; and safeguard efficient

and effective implementation of MSWM practices in the framework of integrated environmental management as well. This shortfall is

partly due to the decentralisation of waste management issues to local authorities without a parallel substantial budgetary and capacity

support, thus resulting in local activity remaining often disoriented and isolated from national strategies, therefore yielding significant

planning and implementation problems and delays against pressing issues at hand as well as loss or poor use of available funds. This paper

develops a systemic approach for MSWM at both the household and the non-household level, summarizes state-of-the-art available tools

and compiles a set of guidelines for developing waste management master plans at the municipal level. It aims to provide a framework inthe MSWM field for municipalities in Greece as well as other countries facing similar problems under often comparable socioeconomic

settings.

10 One-Step Generation of Mice Carrying Reporter and Conditional Alleles by CRISPR/Cas-Mediated Genome Engineering

Summary

The type II bacterial CRISPR/Cas system is a novel genome-engineering technology with the ease of multiplexed gene targeting. Here, we

created reporter and conditional mutant mice by coinjection of zygotes with Cas9 mRNA and different guide RNAs (sgRNAs) as well as

DNA vectors of different sizes. Using this one-step procedure we generated mice carrying a tag or a fluorescent reporter construct in

the Nanog, theSox2, and the Oct4 gene as well as Mecp2 conditional mutant mice. In addition, using sgRNAs targeting two separate sites

in the Mecp2 gene, we produced mice harboring the predicted deletions of about 700 bps. Finally, we analyzed potential off-targets of

five sgRNAs in gene-modified mice and ESC lines and identified off -target mutations in only rare instances.

11 The Hallmarks of Cancer

After a quarter century of rapid advances, cancer research has generated a rich and complex body of knowledge, revealing cancer to be a

disease involving dynamic changes in the genome. The foundation has been set in the discovery of mutations that produce oncogenes

with dominant gain of function and tumor suppressor genes with recessive loss of function; both classes of cancer genes have been
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identified through their alteration in human and animal cancer cells and by their elicitation of cancer phenotypes in experimental models

(Bishop and Weinberg 1996).

Some would argue that the search for the origin and treatment of this disease will continue over the next quarter century in much the

same manner as it has in the recent past, by adding further layers of complexity to a scientific literature that is already complex almost

beyond measure. But we anticipate otherwise: those researching the cancer problem will be practicing a dramatically different type of

science than we have experienced over the past 25 years. Surely much of this change will be apparent at the technical level. But

ultimately, the more fundamental change will be conceptual.We foresee cancer research developing into a logical science, where the complexities of the disease, described in the laboratory and clinic,

will become understandable in terms of a small number of underlying principles. Some of these principles are even now in the midst of

being codified. We discuss one set of them in the present essay: rules that govern the transformation of normal human cells into

malignant cancers. We suggest that research over the past decades has revealed a small number of molecular, biochemical, and cellular

traitsacquired capabilitiesshared by most and perhaps all types of human cancer. Our faith in such simplification derives directly from

the teachings of cell biology that virtually all mammalian cells carry a similar molecular machinery regulating their proliferation,

differentiation, and death.

12 Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

Summary

Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expressionprogram of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer

domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers

that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription

factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause

preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression

programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific

master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of

mammalian cell identity.

13 Imperfect information in a quality-competitive hospital market

Abstract

We examine the implications of policies to improve information about the qualities of profit-seeking duopoly hospitals which face the

same regulated price and compete on quality. We show that if hospital costs of quality are similar then better information increases the

quality of both hospitals. However, if the costs are sufficiently different improved information will reduce the quality of both hospitals.

Moreover, even when quality increases, better information may increase or decrease patient welfare depending on whether an ex post or

ex ante view of welfare is taken.
http://www.sciencedirect.com/science/article/pii/S0092867400816839#BIB6http://www.sciencedirect.com/science/article/pii/S0092867400816839#BIB6http://www.sciencedirect.com/science/article/pii/S0092867400816839#BIB6http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5kYf2qFnMIDFIkFw1RHaqHHjy5mN9v3PWGyg6fWMpMb0aElpmGwnfdSrhmg1trcovGUuGmOUhr5HvArsOaikiJcqrAgeppG17cdYufJ28ZJz094p.CHDwA49http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5kYf2qFnMIDFIkFw1RHaqHHjy5mN9v3PWGyg6fWMpMb0aElpmGwnfdSrhmg1trcovGUuGmOUhr5HvArsOaikiJcqrAgeppG17cdYufJ28ZJz094p.CHDwA49http://elsevier.dmdelivery.com/x/c/?ZYpbCoQwDABvZNpA092FnMIDiMRCw9YHtdDjRz.8cz5nRhht5Y_3yhjJRWeFMQTLnFs7fgC99_EUTZukRWuSNsi_wmNgrk2lJDhUYXSeIuGXvLuhgLZw0e0.3dP0ihcA08http://elsevier.dmdelivery.com/x/c/?ZYpbCoQwDABvZNpA092FnMIDiMRCw9YHtdDjRz.8cz5nRhht5Y_3yhjJRWeFMQTLnFs7fgC99_EUTZukRWuSNsi_wmNgrk2lJDhUYXSeIuGXvLuhgLZw0e0.3dP0ihcA08http://elsevier.dmdelivery.com/x/c/?ZYpbCoQwDABvZNpA092FnMIDiMRCw9YHtdDjRz.8cz5nRhht5Y_3yhjJRWeFMQTLnFs7fgC99_EUTZukRWuSNsi_wmNgrk2lJDhUYXSeIuGXvLuhgLZw0e0.3dP0ihcA08http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5kYf2qFnMIDFIkFw1RHaqHHjy5mN9v3PWGyg6fWMpMb0aElpmGwnfdSrhmg1trcovGUuGmOUhr5HvArsOaikiJcqrAgeppG17cdYufJ28ZJz094p.CHDwA49http://www.sciencedirect.com/science/article/pii/S0092867400816839#BIB6


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14 Betatrophin: A Hormone that Controls Pancreatic @b Cell Proliferation

Summary

Replenishing insulin-producing pancreaticcell mass will benefit both type I and type II diabetics. In adults, pancreaticcells are

generated primarily by self-duplication. We report on a mouse model of insulin resistance that induces dramatic pancreaticcell

proliferation andcell mass expansion. Using this model, we identify a hormone, betatrophin, that is primarily expressed in liver and fat.

Expression of betatrophin correlates with cell proliferation in other mouse models of insulin resistance and during gestation. Transient

expression of betatrophin in mouse liver significantly and specifically promotes pancreaticcell proliferation, expandscell mass, and

improves glucose tolerance. Thus, betatrophin treatment could augment or replace insulin injections by increasing the number of

endogenous insulin-producing cells in diabetics.

15 Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression

Summary

Targeted gene regulation on a genome-wide scale is a powerful strategy for interrogating, perturbing, and engineering cellular systems.

Here, we develop a method for controlling gene expression based on Cas9, an RNA-guided DNA endonuclease from a type II CRISPR

system. We show that a catalytically dead Cas9 lacking endonuclease activity, when coexpressed with a guide RNA, generates a DNA

recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor

binding. This system, which we call CRISPR interference (CRISPRi), can efficiently repress expression of targeted genes in Escherichia coli,

with no detectable off-target effects. CRISPRi can be used to repress multiple target genes simultaneously, and its effects are reversible.

We also show evidence that the system can be adapted for gene repression in mammalian cells. This RNA-guided DNA recognition

platform provides a simple approach for selectively perturbing gene expression on a genome-wide scale.

16 Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Summary

Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as

an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific

therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified

premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes.

Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium

quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited

their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar

to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.
http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDADRG2HjJgQq_RQ9AKpMpFiEj9JIOb7pgh3beSNMtvHYW2EKAwa0zOS9JU61nm_A1lr3E427xEVLlNrJscFd4FuqSo5wqsIHcaJxCK5.ITo3kS2cdV.n.zQ.8AIA03http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDADRG2HjJgQq_RQ9AKpMpFiEj9JIOb7pgh3beSNMtvHYW2EKAwa0zOS9JU61nm_A1lr3E427xEVLlNrJscFd4FuqSo5wqsIHcaJxCK5.ITo3kS2cdV.n.zQ.8AIA03http://elsevier.dmdelivery.com/x/c/?ZcpbCoQwDEDRHZk0PuoIWYULKEMsGKwPaqHLz.gxf.7ec4XJdh6dZSY.oEdLTH1vK6_lXBNArbW5ReMhcdEcpTRy7vAv8M1FJUW4VGFG.NA4_M61iOQc2sJJjy08U3jhDwA32http://elsevier.dmdelivery.com/x/c/?ZcpbCoQwDEDRHZk0PuoIWYULKEMsGKwPaqHLz.gxf.7ec4XJdh6dZSY.oEdLTH1vK6_lXBNArbW5ReMhcdEcpTRy7vAv8M1FJUW4VGFG.NA4_M61iOQc2sJJjy08U3jhDwA32http://elsevier.dmdelivery.com/x/c/?ZcpLCoAwDADRG5m0WqtCTuEBRGLBYP1QCz1_dOHO7bxhsrpTZzSR9S161EjWOV1pzfkaAEop1c0SDg6LpMC54nOHr8CcsnAMcInAiNjbrvWNqRGdN6gLRTm26Z2mHz4A92http://elsevier.dmdelivery.com/x/c/?ZcpLCoAwDADRG5m0WqtCTuEBRGLBYP1QCz1_dOHO7bxhsrpTZzSR9S161EjWOV1pzfkaAEop1c0SDg6LpMC54nOHr8CcsnAMcInAiNjbrvWNqRGdN6gLRTm26Z2mHz4A92http://elsevier.dmdelivery.com/x/c/?ZcpLCoAwDADRG5m0WqtCTuEBRGLBYP1QCz1_dOHO7bxhsrpTZzSR9S161EjWOV1pzfkaAEop1c0SDg6LpMC54nOHr8CcsnAMcInAiNjbrvWNqRGdN6gLRTm26Z2mHz4A92http://elsevier.dmdelivery.com/x/c/?ZcpbCoQwDEDRHZk0PuoIWYULKEMsGKwPaqHLz.gxf.7ec4XJdh6dZSY.oEdLTH1vK6_lXBNArbW5ReMhcdEcpTRy7vAv8M1FJUW4VGFG.NA4_M61iOQc2sJJjy08U3jhDwA32http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDADRG2HjJgQq_RQ9AKpMpFiEj9JIOb7pgh3beSNMtvHYW2EKAwa0zOS9JU61nm_A1lr3E427xEVLlNrJscFd4FuqSo5wqsIHcaJxCK5.ITo3kS2cdV.n.zQ.8AIA03


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17 Business Models, Business Strategy and Innovation

Whenever a business enterprise is established, it either explicitly or implicitly employs a particular business model that describes the

design or architecture of the value creation, delivery, and capture mechanisms it employs. The essence of a business model is in defining

the manner by which the enterprise delivers value to customers, entices customers to pay for value, and converts those payments to

profit. It thus reflects management's hypothesis about what customers want, how they want it, and how the enterprise can organize to

best meet those needs, get paid for doing so, and make a profit. The purpose of this article is to understand the significance of business

models and explore their connections with business strategy, innovation management, and economic theory.18 Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity

Summary

Targeted genome editing technologies have enabled a broad range of research and medical applications. The Cas9 nuclease from the

microbial CRISPR-Cas system is targeted to specific genomic loci by a 20 nt guide sequence, which can tolerate certain mismatches to the

DNA target and thereby promote undesired off-target mutagenesis. Here, we describe an approach that combines a Cas9 nickase mutant

with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity,

simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and extends the number of specifically

recognized bases for target cleavage. We demonstrate that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell

lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency. This versatile strategy enables a

wide variety of genome editing applications that require high specificity.

19 ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering

Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) comprise a powerful class of tools that are

redefining the boundaries of biological research. These chimeric nucleases are composed of programmable, sequence-specific DNA-

binding modules linked to a nonspecific DNA cleavage domain. ZFNs and TALENs enable a broad range of genetic modifications by

inducing DNA double-strand breaks that stimulate error-prone nonhomologous end joining or homology-directed repair at specific

genomic locations. Here, we review achievements made possible by site-specific nuclease technologies and discuss applications of these

reagents for genetic analysis and manipulation. In addition, we highlight the therapeutic potential of ZFNs and TALENs and discuss future

prospects for the field, including the emergence of clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-

guided DNA endonucleases.

20 Social media? Get serious! Understanding the functional building blocks of social media

Abstract

Traditionally, consumers used the Internet to simply expend content: they read it, they watched it, and they used it to buy products and

services. Increasingly, however, consumers are utilizing platformssuch as content sharing sites, blogs, social networking, and wikisto

create, modify, share, and discuss Internet content. This represents the social media phenomenon, which can now significantly impact a

firm's reputation, sales, and even survival. Yet, many executives eschew or ignore this form of media because they dont understand

what it is, the various forms it can take, and how to engage with it and learn. In response, we present a framework that defines social
http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDEXRHeGX0EBbyavohBlCJhJWw0chUpbvMuiM6T1X2NvKT2eZfd_hhyX2IdjCSynHm6jW2pyicZM4a45SGtlX_heaclFJkQ5V_gD_0bVweAEIbrCZk27f8ZrGG.4AA99http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDEXRHeGX0EBbyavohBlCJhJWw0chUpbvMuiM6T1X2NvKT2eZfd_hhyX2IdjCSynHm6jW2pyicZM4a45SGtlX_heaclFJkQ5V_gD_0bVweAEIbrCZk27f8ZrGG.4AA99http://elsevier.dmdelivery.com/x/c/?ZYxbCoAgEABv1K5WWsGeogNIrEJL9sAEj2999NfvzDBMuu40qJpIW4MWayTd93WlNedrAiilNDdLODh4SYFzw_cOH4ElZeEY4BKBGXHUg7GdalGheieeohybeyP3kw8A72http://elsevier.dmdelivery.com/x/c/?ZYxbCoAgEABv1K5WWsGeogNIrEJL9sAEj2999NfvzDBMuu40qJpIW4MWayTd93WlNedrAiilNDdLODh4SYFzw_cOH4ElZeEY4BKBGXHUg7GdalGheieeohybeyP3kw8A72http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5m00kYHcgoPIBILhqk.1EKPH13Mbrbve8Ledh6cFfYUkdAy_xBs463W6wPQWutu0XRIWrUkqZ2cO.wKLKWq5ASXKkzoIhGNo_sRcaBgK2c9vvM7zX.4AAA13http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5m00kYHcgoPIBILhqk.1EKPH13Mbrbve8Ledh6cFfYUkdAy_xBs463W6wPQWutu0XRIWrUkqZ2cO.wKLKWq5ASXKkzoIhGNo_sRcaBgK2c9vvM7zX.4AAA13http://elsevier.dmdelivery.com/x/c/?ZYpJCoAwDAB.ZJKKrQh5hQ8QiQWDdaEW_vzowZu3YWaEne3ck2V2wWNAS_y6zlZeS7kGgFprc4vGQ_KiOUpp5NzhMzDnopIiXKowImLwPbVEL6EnWzjpsU3vNP3iAwA59http://elsevier.dmdelivery.com/x/c/?ZYpJCoAwDAB.ZJKKrQh5hQ8QiQWDdaEW_vzowZu3YWaEne3ck2V2wWNAS_y6zlZeS7kGgFprc4vGQ_KiOUpp5NzhMzDnopIiXKowImLwPbVEL6EnWzjpsU3vNP3iAwA59http://elsevier.dmdelivery.com/x/c/?ZYpJCoAwDAB.ZJKKrQh5hQ8QiQWDdaEW_vzowZu3YWaEne3ck2V2wWNAS_y6zlZeS7kGgFprc4vGQ_KiOUpp5NzhMzDnopIiXKowImLwPbVEL6EnWzjpsU3vNP3iAwA59http://elsevier.dmdelivery.com/x/c/?ZcpNCoQwDEDhG5m00kYHcgoPIBILhqk.1EKPH13Mbrbve8Ledh6cFfYUkdAy_xBs463W6wPQWutu0XRIWrUkqZ2cO.wKLKWq5ASXKkzoIhGNo_sRcaBgK2c9vvM7zX.4AAA13http://elsevier.dmdelivery.com/x/c/?ZYxbCoAgEABv1K5WWsGeogNIrEJL9sAEj2999NfvzDBMuu40qJpIW4MWayTd93WlNedrAiilNDdLODh4SYFzw_cOH4ElZeEY4BKBGXHUg7GdalGheieeohybeyP3kw8A72http://elsevier.dmdelivery.com/x/c/?ZcpLDoMwDEXRHeGX0EBbyavohBlCJhJWw0chUpbvMuiM6T1X2NvKT2eZfd_hhyX2IdjCSynHm6jW2pyicZM4a45SGtlX_heaclFJkQ5V_gD_0bVweAEIbrCZk27f8ZrGG.4AA99


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media by using seven functional building blocks: identity, conversations, sharing, presence, relationships, reputation, and groups. As

different social media activities are defined by the extent to which they focus on some or all of these blocks, we explain the implications

that each block can have for how firms should engage with social media. To conclude, we present a number of recommendations

regarding how firms should develop strategies for monitoring, understanding, and responding to different social media activities.

21 CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes

SummaryThe genetic interrogation and reprogramming of cells requires methods for robust and precise targeting of genes for expression or

repression. The CRISPR-associated catalytically inactive dCas9 protein offers a general platform for RNA-guided DNA targeting. Here, we

show that fusion of dCas9 to effector domains with distinct regulatory functions enables stable and efficient transcriptional repression or

activation in human and yeast cells, with the site of delivery determined solely by a coexpressed short guide (sg)RNA. Coupling of dCas9 to

a transcriptional repressor domain can robustly silence expression of multiple endogenous genes. RNA-seq analysis indicates that CRISPR

interference (CRISPRi)-mediated transcriptional repression is highly specific. Our results establish that the CRISPR system can be used as a

modular and flexible DNA-binding platform for the recruitment of proteins to a target DNA sequence, revealing the potential of CRISPRi as

a general tool for the precise regulation of gene expression in eukaryotic cells.

22 High temperature long term stability of SiC Schottky diodes

AbstractReliability of Silicon Carbide (SiC) power devices is still an open problem, preventing a wider application of such a promising technology.

Moreover, specific reliability assessment procedures must be developed for SiC devices, as they are designed to work at temperatures

well beyond those of standard Silicon devices. A detailed investigation about the reliability of 600 V, 6 A Silicon Carbide Schottky diodes is

accomplished along this paper. It is based on an extensive set of high temperature reverse bias endurance tests, performed on devices

featuring different packages. Only small forward voltage drop and reverse current drifts have been recorded after a 1000 h long test,

confirming the parametric stability and the reliability level reached by last generation SiC Schottky diodes. Moreover, devices assembled

in TO220 package without flame retardant components in the molding compound performed better than devices assembled in other

TO220 packages, or assembled in hermetic TO3 package, pointing out the role played by the interface between the green molding

compound and the top passivation layer in the long term parametric stability.

23 Synthesis of graphene-based nanosheets via chemical reduction of exfoliated graphite oxideAbstract

Reduction of a colloidal suspension of exfoliated graphene oxide sheets in water with hydrazine hydrate results in their aggregation and

subsequent formation of a high-surface-area carbon material which consists of thin graphene-based sheets. The reduced material was

characterized by elemental analysis, thermo-gravimetric analysis, scanning electron microscopy, X-ray photoelectron spectroscopy, NMR

spectroscopy, Raman spectroscopy, and by electrical conductivity measurements.
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24 Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of

Disease Study 2010

Summary

Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health

policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths

for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex.

25 College students' social networking experiences on Facebook

Abstract

Millions of contemporary young adults use social networking sites. However, little is known about how much, why, and how they use

these sites. In this study, 92 undergraduates completed a diary-like measure each day for a week, reporting daily time use and responding

to an activities checklist to assess their use of the popular social networking site, Facebook. At the end of the week, they also completed a

follow-up survey. Results indicated that students use Facebook approximately 30 min throughout the day as part of their daily routine.

Students communicated on Facebook using a one-to-many style, in which they were the creators disseminating content to their friends.

Even so, they spent more time observing content on Facebook than actually posting content. Facebook was used most often for social

interaction, primarily with friends with whom the students had a pre-established relationship offline. In addition to classic identity

markers of emerging adulthood, such as religion, political ideology, and work, young adults also used media preferences to express their

identity. Implications of social networking site use for the development of identity and peer relationships are discussed.
http://elsevier.dmdelivery.com/x/c/?ZcpLCoUwDEDRHZk0aitCVuEC5BELBuuHWujy4xs4c3rPFSbbeXCWmYLHgJaY_t5WXku5RoBaa3OLxkPiojlKaeTc4S3wy0UlRbhUYULXoQ_td_RdoAFt4aTHNv_n_YMPA14http://elsevier.dmdelivery.com/x/c/?ZcpLCoUwDEDRHZk0aitCVuEC5BELBuuHWujy4xs4c3rPFSbbeXCWmYLHgJaY_t5WXku5RoBaa3OLxkPiojlKaeTc4S3wy0UlRbhUYULXoQ_td_RdoAFt4aTHNv_n_YMPA14http://elsevier.dmdelivery.com/x/c/?ZcpLCoUwDEDRHZk0aitCVuEC5BELBuuHWujy4xs4c3rPFSbbeXCWmYLHgJaY_t5WXku5RoBaa3OLxkPiojlKaeTc4S3wy0UlRbhUYULXoQ_td_RdoAFt4aTHNv_n_YMPA14http://elsevier.dmdelivery.com/x/c/?ZcrBDcMgDEDRjWIDTSCVPEUHQJGDhFVII4rE_E4OvfX632eyWikYbWT9gh61kJ1nzZR7P58AY4zpy5IOTru0xH3iT4Vfga114ZLgFIEXmtW51TsMiOaBQXcqcrzjPcU.vAAA13http://elsevier.dmdelivery.com/x/c/?ZcrBDcMgDEDRjWIDTSCVPEUHQJGDhFVII4rE_E4OvfX632eyWikYbWT9gh61kJ1nzZR7P58AY4zpy5IOTru0xH3iT4Vfga114ZLgFIEXmtW51TsMiOaBQXcqcrzjPcU.vAAA13http://elsevier.dmdelivery.com/x/c/?ZcrBDcMgDEDRjWIDTSCVPEUHQJGDhFVII4rE_E4OvfX632eyWikYbWT9gh61kJ1nzZR7P58AY4zpy5IOTru0xH3iT4Vfga114ZLgFIEXmtW51TsMiOaBQXcqcrzjPcU.vAAA13http://elsevier.dmdelivery.com/x/c/?ZcpLCoUwDEDRHZk0aitCVuEC5BELBuuHWujy4xs4c3rPFSbbeXCWmYLHgJaY_t5WXku5RoBaa3OLxkPiojlKaeTc4S3wy0UlRbhUYULXoQ_td_RdoAFt4aTHNv_n_YMPA14http://elsevier.dmdelivery.com/x/c/?ZcpLCoUwDEDRHZk0aitCVuEC5BELBuuHWujy4xs4c3rPFSbbeXCWmYLHgJaY_t5WXku5RoBaa3OLxkPiojlKaeTc4S3wy0UlRbhUYULXoQ_td_RdoAFt4aTHNv_n_YMPA14

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